Comparison of Clinical Outcomes in the Slow-Developing Blastocysts With or Without Preimplantation Genetic Testing-Aneuploidy on Day 6 in the Frozen-Thawed Cycle.

OBJECTIVE: This study investigated the potential of the slow-developing blastocysts using preimplantation genetic testing-aneuploidy (PGT-A) in patients undergoing frozen-thawed embryo transfer, stratified by age. STUDY DESIGN: A retrospective analysis was performed including a total of 743, the first frozen embryo transfer (FET) cycle with single embryo transfer (SET), who underwent treatment between January 2020 and July 2023 in a single fertility center, XXXX Fertility Center. A total of 743 cycles, in which we performed intracellular sperm injection and freeze all strategy, from 743 patients were included. The patient group was divided into 4 groups as follows: Group 1 (G1), 208 FET on day 5; Group 2 (G2), 177 FET with PGT-A on day 5; Group 3 (G3), 220 FET on day 6; Group 4 (G4), 138 FET with PGT-A on day 6. We also divided into two groups-under 35 years of age and over 35 years of age-and performed the analysis separately for each group. RESULTS: In under 35 years of age groups, there were no significant differences in clinical pregnancy and miscarriage rates in G1 and G2 (67.2% vs 63.8%, NS). Also, G4 had a higher clinical pregnancy rate than G3, but it was not significant (51.8% vs 54.7%, NS). In 35 years or older group, G2 had higher pregnancy rates than G1 and lower miscarriage rates (CPR: 43.3% vs 67.7%, P = 0.001, MR: 22.5% vs 3.4%, P = 0.001). In addition, G4 had a higher pregnancy rate than G3 and lower miscarriage rate (CPR: 31.8% vs. 46.9%, P = 0.003, MR: 22.9% vs 2.2%, P = 0.023). CONCLUSIONS: In ≥35 years group, PGT-A on day 5 and day 6 showed a high pregnancy rate and a low miscarriage rate. Therefore, using PGT-A seems advantageous for patients of an advanced maternal age.

The Analysis of in vitro Fertilization Outcomes after Fertility-Preserving Therapy for Endometrial Hyperplasia or Carcinoma.

OBJECTIVES: This study aimed to evaluate the clinical efficacy of fertility-preserving therapy through in vitro fertilization (IVF) procedures in women who were pathologically diagnosed with endometrial hyperplasia or carcinoma. DESIGN: A retrospective cohort study on fertility-preserving therapy was conducted. Participants/Materials, Setting: A total of 82 women were enrolled who had simple endometrial hyperplasia (SH), complex hyperplasia (CH), complex atypical hyperplasia (CAH), and endometrioid endometrial carcinoma stage IA (EC IA) and underwent IVF at Gangnam CHA fertility center between January 2008 and December 2020. METHODS: The primary endpoints were oncologic outcomes and subsequent reproductive outcomes of patients who underwent fertility-preserving treatments analyzed by χ2 test or Fisher's exact test. RESULTS: Of the 82 patients, 33 had a cumulative clinical pregnancy (40.2%), and 25 had a cumulative live birth (30.5%) through IVF procedures following pathologic confirmation of complete remission or non-progressive status. The cumulative clinical pregnancy rates and live birth rates for SH were 50.0% and 30.0%, for CH were 37.8% and 28.9%, for CAH were 25.0% and 25.0%, and for EC were 38.5% and 38.5%, respectively. There were no significant differences in cumulative clinical pregnancy rates or live birth rates when comparing the four groups. There was a difference in endometrial thickness between medroxyprogesterone acetate (MPA) treatment group and intrauterine device (IUD) group (p = 0.036); however, there were no significant differences in clinical pregnancy rates among MPA, IUD, and MPA+IUD groups. LIMITATIONS: Because of the retrospective nature of the study, many factors relevant to the treatment decision were not strictly controlled. CONCLUSIONS: All endometrial hyperplasia and carcinoma groups had competent cumulative live birth rates by IVF procedures. There may be differences in endometrial thickness depending on the treatment methods, but this does not affect clinical pregnancy rates. Therefore, the fertility-preserving treatment for endometrial hyperplasia and carcinoma is a safe and feasible method that results in good IVF outcomes.

Predictive model of IVF outcomes for polycystic ovarian morphology and polycystic ovary syndrome in GnRH antagonist protocol using AMH-MoM and ovarian sensitivity index.

AIM: To evaluate the relationship between AMH and ovarian response to controlled ovarian hyperstimulation in women with PCOM and PCOS. METHODS: A retrospective study was conducted on 559 patients who underwent the IVF-ET cycle between January 2018 and December 2022 at Gangnam Cha Hospital. Patients were divided into 3 groups matched for age and BMI: the PCOS group (n = 54), based on the new 2023 PCOS guideline; the PCOM group (n = 53); and the control group (n = 452) with normal ovaries. Serum AMH levels were converted to multiples of the median (MoM) for each corresponding age. The ovarian sensitivity index (OSI) was calculated as the number of retrieved oocytes divided by the total dose of recombinant FSH administered (per 1000 IU). RESULTS: There were significant differences in AMH-MoM value among women with PCOS [2.7 ± 1.3 (95% CI 2.3-3.0)], those with PCOM [2.0 ± 1.0 (95% CI 1.7-2.3)], and controls [0.8 ± 0.7 (95% CI 0.8-0.9)] (p < 0.001). The abortion rates in the normoovulatory, PCOM, and PCOS groups were 18.2%, 21.1%, and 25.0%, respectively. OSI and live birth rate were positively correlated with the AMH-MoM value in normoovulatory women (r = 0.389, p < 0.05, r = 0.122, p < 0.05), while no such correlation was observed in women with PCOM and PCOS. CONCLUSIONS: Ovarian response and live birth rate are possibly correlated with the AMH-MoM value in normoovulatory women, but not in women with PCOM and PCOS.

Pre-conditioning modifies the TME to enhance solid tumor CAR T cell efficacy and endogenous protective immunity.

Chimeric antigen receptor (CAR) T cell therapy has led to impressive clinical responses in patients with hematological malignancies; however, its effectiveness in patients with solid tumors has been limited. While CAR T cells for the treatment of advanced prostate and pancreas cancer, including those targeting prostate stem cell antigen (PSCA), are being clinically evaluated and are anticipated to show bioactivity, their safety and the impact of the immunosuppressive tumor microenvironment (TME) have not been faithfully explored preclinically. Using a novel human PSCA knockin (hPSCA-KI) immunocompetent mouse model, we evaluated the safety and therapeutic efficacy of PSCA-CAR T cells. We demonstrated that cyclophosphamide (Cy) pre-conditioning significantly modified the immunosuppressive TME and was required to uncover the efficacy of PSCA-CAR T cells in metastatic prostate and pancreas cancer models, with no observed toxicities in normal tissues with endogenous expression of PSCA. This combination dampened the immunosuppressive TME, generated pro-inflammatory myeloid and T cell signatures in tumors, and enhanced the recruitment of antigen-presenting cells, as well as endogenous and adoptively transferred T cells, resulting in long-term anti-tumor immunity.

Efficacy and safety of newly developed ganirelix acetate in infertile women for assisted reproductive technology: a prospective, randomised, controlled study.

This study aimed to investigate the efficacy of Ganilever pre-filled syringe (PFS), a newly developed ganirelix acetate, for the inhibition of premature luteinising hormone (LH) surge in in vitro fertilisation (IVF). A prospective randomised controlled study was conducted (NCT03051087). A total of 236 women (Ganilever group: 114, Orgalutran group: 122) were finally analysed. The patients with LH of >10 mIU/mL on the day of human chorionic gonadotropin (hCG) injection were 0 (0.0%) and 3 (2.5%) in the Ganilever and Orgalutran groups, respectively (p= .25). The number of retrieved oocytes from two groups did not show any significant difference (12.0 ± 6.4 vs. 11.8 ± 6.3, p= .73). Furthermore, the two groups did not show significant differences in the number of good-quality oocytes and embryo, and the rate of fertilisation. Similar safety profiles were also observed. In conclusion, Ganilever PFS showed comparable IVF outcomes and safety profile in IVF, as compared to the Orgalutran. Impact StatementWhat is already known on this subject? Premature LH surge during controlled ovarian stimulation results in the induction of luteinisation of the immature follicles. Thus, gonadotrophin-releasing hormone (GnRH) antagonist protocol was suggested as an option for suppression of premature LH surge. Currently, one of GnRH antagonists being widely used is ganirelix acetate (Orgalutran®; Organon, Oss, The Netherlands). Ganilever pre-filled syringe (PFS) is a newly developed GnRH antagonist containing ganirelix acetate as an active ingredient.What do the results of this study add? Our study demonstrated that Ganilever PFS showed comparable IVF outcomes and patient safety profile in infertile women undergoing in IVF-ET, as compared to the Orgalutran.What are the implications of these findings for clinical practice and/or further research? The results of our study will provide another available GnRH antagonist to be used in patients with IVF.

Erratum: Correction of Author ORCID in the Article: Efficacy of Random-start Controlled Ovarian Stimulation in Cancer Patients.

This corrects the article on p. 290 in vol. 30, PMID: 25729252.

A Kaposi's Sarcoma-Associated Herpesvirus Infection Mechanism Is Independent of Integrins α3ß1, αVß3, and αVß5.

Host receptor usage by Kaposi's sarcoma-associated herpesvirus (KSHV) has been best studied using primary microvascular endothelial and fibroblast cells, although the virus infects a wide variety of cell types in culture and in natural infections. In these two infection models, KSHV adheres to the cell though heparan sulfate (HS) binding and then interacts with a complex of EphA2, xCT, and integrins α3ß1, αVß3, and αVß5 to catalyze viral entry. We dissected this receptor complex at the genetic level with CRISPR-Cas9 to precisely determine receptor usage in two epithelial cell lines. Surprisingly, we discovered an infection mechanism that requires HS and EphA2 but is independent of αV- and ß1-family integrin expression. Furthermore, infection appears to be independent of the EphA2 intracellular domain. We also demonstrated that while two other endogenous Eph receptors were dispensable for KSHV infection, transduced EphA4 and EphA5 significantly enhanced infection of cells lacking EphA2.IMPORTANCE Our data reveal an integrin-independent route of KSHV infection and suggest that multiple Eph receptors besides EphA2 can promote and regulate infection. Since integrins and Eph receptors are large protein families with diverse expression patterns across cells and tissues, we propose that KSHV may engage with several proteins from both families in different combinations to negotiate successful entry into diverse cell types.

Correlation between Morphologic Grading and Euploidy Rates of Blastocysts, and Clinical Outcomes in In Vitro Fertilization Preimplantation Genetic Screening.

BACKGROUND: The standard morphological evaluation has been widely used for embryo selection, but it has limitations. This study aimed to investigate the correlation between morphologic grading and euploidy rate of in vitro fertilization (IVF) preimplantation genetic screening (PGS) and compare the pregnancy rates in young and old ages. METHODS: This is a retrospective study using the medical records of patients who underwent IVF procedures with PGS between January 2016 and February 2017 in a single center. The embryo grades were categorized into 4 groups: excellent, good, fair, and poor. Basic characteristics, euploidy rates, clinical pregnancy (CP) rates and ongoing pregnancy rates were analyzed. RESULTS: The excellent group had significantly higher rate of euploid embryos than fair group (47.82% vs. 29.33%; P = 0.023) and poor group (47.82% vs. 29.60%; P = 0.005). When the four groups were recategorized into two groups (excellent and good vs. fair and poor), they also showed significant difference in euploidy rates (44.52% vs. 29.53%; P = 0.002). When the patients were divided into two groups by age 35, the CP rates for those under and over 35 years old were 44.74% and 47.83%, respectively, which showed no significant difference. CONCLUSION: The significant differences among the euploidy rates of different morphologic embryo grades demonstrated the positive correlations between the morphologic grading of the embryo and the euploidy rate of PGS. Additionally, there was no significant difference between the younger and older patients' CP rates. These findings emphasize the fact that old age patients might benefit from PGS whatever the indication of PGS is.

Effects and pregnancy outcomes of L-carnitine supplementation in culture media for human embryo development from in vitro fertilization.

AIM: Antioxidants have been studied to be effective in improving embryo qualities from in vitro fertilization. L-carnitine (LC) has been known to reduce reactive oxygen species and enhance adenosine triphosphate production, which contribute to the development of a high-quality embryo. This is the first study to include both mouse and human subjects and aimed to evaluate whether LC supplementation in culture media has any beneficial effect on the development of the embryos, as well as its clinical outcomes. METHODS: Mouse embryos were used as models in the animal studies for cell immunofluorescent staining evaluation. Inner cell mass and trophectoderm (TE) cells were counted and statistically analyzed between LC and control groups. For human studies, medical records of patients with infertility undergoing in vitro fertilization procedures from January to May 2017 were included and the embryos were divided into two groups at the two pronuclear stage. Statistical analysis was performed to compare the embryo status and clinical outcomes of the two groups. RESULTS: In the animal study, the LC group showed significantly higher numbers of cells in the inner cell mass and trophectoderm, indicating better development. In the human studies, there were significantly higher numbers of good-quality embryos on days 2, 3 and 5 in the LC group than in the control. The clinical outcomes, such as implantation, clinical pregnancy and ongoing pregnancy rates, were also higher in the LC group than in the control. CONCLUSION: LC supplementation in culture media improved human embryo quality and eventually achieved better pregnancy outcomes.

Increased proportion of mature oocytes with sustained-release growth hormone treatment in poor responders: a prospective randomized controlled study.

PURPOSE: Supplementation of growth hormone (GH) during controlled ovarian stimulation (COS) has been suggested to improve ovarian response. Despite potential benefits in poor responders, multiple injections of GH during COS are inconvenient. We conducted a randomized controlled study to evaluate the efficacy and safety of sustained-release human GH in poor responders undergoing in vitro fertilization (IVF). METHODS: This was a single-center, randomized, open-label, parallel study. Infertile women who satisfied the Bologna criteria for poor responders were randomized into GH treatment and control groups. The treatment group received a sustained-release GH (Eutropin Plus® 20 mg) three times before and during COS (mid-luteal, late luteal, and menstrual cycle day 2). The baseline characteristics and IVF outcomes were compared between the two groups. RESULTS: A total of 127 patients were included in the analysis. The mean age was 39.6 years and mean anti-Müllerian hormone level was 0.6 ng/ml. There was no significant difference in the baseline characteristics between GH treatment and control groups. The number of follicles on the human chorionic gonadotropin triggering day (3.1 ± 2.3 vs. 2.4 ± 1.6, P = 0.043) and the proportion of metaphase II oocytes (67.5 vs. 52.3%, P = 0.030) were higher in the GH group than in controls. The percentage of clinical and ongoing pregnancy and miscarriage was not different between the two groups. CONCLUSION: Supplementation of sustained-release GH before and during COS improved ovarian response, with an increase in mature oocytes in poor responders. Further studies are needed to ensure this benefit in general infertility patients.

Expressions of aquaporin family in human luteinized granulosa cells and their correlations with IVF outcomes.

STUDY QUESTION: Are mRNAs for specific aquaporins (AQPs) expressed in human luteinized granulosa cells (GCs) and are their expression levels correlated with in vitro fertilization (IVF) outcomes? SUMMARY ANSWER: The mRNAs of AQP1-7, 9, 11, and 12 were expressed in human luteinized GCs; the level of AQP1 mRNA was negatively associated with retrieved oocyte number and the level of AQP7 mRNA was positively associated with fertilization rate. WHAT IS KNOWN ALREADY: mRNAs of AQP1-4 and AQP9 have been detected in human GCs. STUDY DESIGN, SIZE, DURATION: Prospective observational study involving 111 women undergoing a stimulated IVF cycle. PARTICIPANTS/MATERIALS, SETTING, METHODS: In a preliminary experiment on 27 women, the mRNA expression of AQP0-12 in GCs was explored by RT-PCR. In the main experiment, luteinized GCs were obtained from 111 women at the time of oocyte retrieval of whom 102 had an embryo replacement. Real-time quantitative RT-PCR (qRT-PCR) was performed to quantify the mRNA level of AQP1-7, 9, 11, and 12. The mRNA for luteinizing hormone receptor (LHR) and steroidogenic acute regulatory protein (StAR) were also quantified by qRT-PCR. MAIN RESULTS AND THE ROLE OF CHANCE: mRNAs for AQP0, 8 and 10 were not detected in the preliminary experiment. In samples from 111 women, retrieved oocyte number was negatively associated with the mRNA levels of AQP1, 4, 6, and 11 and LHR (r = -0.311, r = -0.233, r = -0.203, r = -0.194, and r = -0.202, respectively, P < 0.05 for each), however, after adjustment for woman's age and serum anti-Müllerian hormone (AMH) levels, only correlation with AQP1 was found (r = -0.299, P < 0.05). BMI was negatively associated (after adjustment for age) with the mRNA level of AQP7 (r = -0.259, P < 0.05). Fertilization rate was positively associated with the mRNA level of AQP7 (r = 0.269, P < 0.05). The number or quality of embryos or clinical pregnancy was not associated with the mRNA levels of any of ten AQP subtypes. The mRNA levels for the ten AQP subtypes were correlated positively with LHR expression but negatively with StAR expression. Amongst high responders (oocyte number ≥14), the mRNA levels of AQP11 (1.4 ± 0.7 versus 1.7 ± 0.6) and LHR (1.3 ± 0.7 versus 1.7 ± 0.7) were significantly lower in the group with PCOS than in the non-PCOS group. LIMITATIONS, REASONS FOR CAUTION: A relative small number of subjects in PCOS group is the main limitation of our study. P-values were not corrected for multiple comparisons. WIDER IMPLICATION OF THE FINDINGS: AQP1 may be one of the factors that modulate individual ovarian response to exogenous gonadotrophin. The mRNA level of AQP7 was positively associated with fertilization rate, which is a surrogate marker of oocyte competence, thus expression of AQP7 could be a marker for adequate folliculogenesis and healthy oocytes. STUDY FUNDING/COMPETING INTERESTS: This work was supported by grant no. A120043 from the Korea Health Care Technology R&D Project, Ministry of Health and Welfare, Korea. None of the authors has any conflict of interest to declare.

Effects of antifreeze proteins on the vitrification of mouse oocytes: comparison of three different antifreeze proteins.

STUDY QUESTION: Can antifreeze proteins (AFPs) from three different sources improve the efficacy of mouse oocyte vitrification? SUMMARY ANSWER: Treatment with AFPs can improve both murine oocyte quality and embryo development, and reduce reactive oxygen species (ROS) production in vitrified-warmed oocytes. WHAT IS KNOWN ALREADY: A previous study discovered that vitrification of immature oocytes and 2-cell stage embryos of mice augmented with antifreeze glycoproteins at 40 mg/ml dramatically improved the morphological integrity of the samples, suggesting that AFPs have the ability to inhibit ice formation and stabilize the plasma membrane. STUDY DESIGN, SIZE, DURATION: Metaphase II oocytes were obtained from 4-week-old BD-F1 mice. AFPs from bacteria (Flavobacterium frigoris ice-binding protein (FfIBP)), yeast (Glaciozyma sp. ice-binding protein (LeIBP)) and fish (Type III AFP) were added to the vitrification and warming solutions individually. Survival and development, meiotic spindle organization, intracellular ROS, mitochondrial activity, DNA double-strand breaks (DSBs) and repair of damaged DNA were analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Vitrification of oocytes was performed with the CryoTop (equilibration solution: 7.5% ethylene glycol (EG) and 7.5% 1,2-propandiol (PROH) for 5 min; vitrification solution: 15% EG, 15% PROH and 0.5 M sucrose for 1 min). Warming was performed in three steps with decreasing concentrations of sucrose (1.0, 0.5 and 0.25 M sucrose). MAIN RESULTS AND THE ROLE OF CHANCE: AFP treatment can improve murine oocyte quality and embryo development. Survival rates, cleavage rates and blastocyst rates (blastocyst per cleaved and per survived oocytes) of oocytes in AFP-treated groups were significantly higher than those in the control group [75.0, 89.0, 90.0 and 85.0% for survival rate (P = 0.012); 58.7, 89.0, 87.8 and 81.2% for cleavage rate (P = 0.003); 52.3, 87.7, 78.5 and 76.8% for blastocyst per cleaved oocytes (P < 0.01); 30.7, 78.0, 68.9 and 62.4% for blastocyst per survived oocytes (P < 0.01) in control, FfIBP, LeIBP and Type III AFP-treated groups, respectively]. The mean (±SD) number of apoptotic blastomeres per blastocyst was significantly lower in AFP-treated groups than in the control group (9.1 ± 1.0, 2.0 ± 1.7, 2.3 ± 1.2 and 2.7 ± 2.4 in control, FfIBP, LeIBP and Type III AFP-treated groups, respectively, P = 0.040). FfIBP treatment was the most effective in maintaining normal meiotic spindle organization and chromosome alignment (52.0, 92.0, 80.0 and 83.0% in control, FfIBP, LeIBP and Type III AFP-treated groups, respectively, P < 0.01). Intracellular ROS levels (mean ± SD) significantly decreased in the AFP-treated groups (17.0 ± 11.2, 8.4 ± 8.2, 10.3 ± 6.4 and 11.6 ± 12.3 in control, FfIBP, LeIBP and Type III AFP-treated groups, respectively, P < 0.01), and the FfIBP and LeIBP groups had significantly lower DNA DSBs, compared with controls (65.2, 30.8, 44.4 and 55.8% in control, FfIBP, LeIBP and Type III AFP-treated groups, respectively, P < 0.01). LIMITATIONS, REASONS FOR CAUTION: The origins of FfIBP and LeIBP were bacteria and yeast, respectively. Therefore, treatment of human oocytes and embryos with these AFPs should be tested before clinical application. WIDER IMPLICATIONS OF THE FINDINGS: After further research, AFPs can potentially be applied to human oocyte cryopreservation to improve the efficacy of vitrification. STUDY FUNDING/COMPETING INTERESTS: This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI12C0055). The authors have no conflict of interest to declare.

Learning Curve Analysis and Surgical Outcomes of Single-port Laparoscopic Myomectomy.

STUDY OBJECTIVE: To identify learning curves for single-port laparoscopic myomectomy (SPLM) and evaluate surgical outcomes according to the sequence of operation. DESIGN: A retrospective study. SETTING: A university-based hospital (Canadian Task Force classification II-2). PATIENTS: The medical records from 205 patients who had undergone SPLM from October 2009 to May 2013 were reviewed. Because the myomectomy time was significantly affected by the size and number of myomas removed by SPLM, cases in which 2 or more of the myomas removed were >7 cm in diameter were excluded. Furthermore, cases involving additional operations performed simultaneously (e.g., ovarian or hysteroscopic surgery) were also excluded. A total of 161 cases of SPLM were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We assessed the SPLM learning curve via a graph based on operation time versus sequence of cases. Patients were chronologically arranged according to their surgery dates and were then placed into 1 of 4 groups according to their operation sequence. SPLM was completed successfully in 160 of 161 cases (99.4%). One case was converted to multiport surgery. Basal characteristics of the patients between the 4 groups did not differ. The median operation times for the 4 groups were 112.0, 92.8, 83.7, and 90.0 minutes, respectively. Operation time decreased significantly in the second, third, and fourth groups compared with that in the first group (p < .001). Proficiency, which is the point at which the slope of the learning curve became less steep, was evident after about 45 operations. CONCLUSION: Results from the current study suggested that proficiency for SPLM was achieved after about 45 operations. Additionally, operation time decreased with experience without an increase in complication rate.

Efficacy of random-start controlled ovarian stimulation in cancer patients.

This study aimed to evaluate the efficacy of random-start controlled ovarian stimulation (COS) in cancer patients for emergency fertility preservation. In this retrospective comparative study, 22 patients diagnosed with cancer and 44 infertile women undergoing conventional in vitro fertilization (IVF) were included. In cancer patients, ovarian stimulation was started on the day of referral, irrespective of their menstrual cycle date. The control group was selected by age matching among women undergoing conventional IVF. COS outcomes were compared between groups. The number of total and mature oocytes retrieved and the oocyte maturity rate were higher in the random-start group than in the conventional-start group. However, duration of ovarian stimulation was longer in the random-start group (11.4 vs. 10.3 days, P = 0.004). The addition of letrozole to lower the estradiol level during COS did not adversely affect total oocytes retrieved. However, oocyte maturity rate was lower in cycles with letrozole than in cycles without letrozole (71.6% vs. 58.2%, P = 0.019). Our study confirms the feasibility and effectiveness of random-start COS in cancer patients.

The beneficial effects of polyethylene glycol-superoxide dismutase on ovarian tissue culture and transplantation.

PURPOSE: Reducing the ischemic damage from free radicals that is inflicted on ovarian tissue is critical for successful ovarian tissue transplantation. Polyethylene glycol-superoxide dismutase (PEG-SOD) is mimetic of superoxide dismutase (SOD) and powerful free radical scavenger acts by reducing superoxide anions. The objective of study was to evaluate effects of PEG-SOD on mouse ovarian tissues in in vitro culture and in autotransplantation. METHODS: Ovaries were collected and randomly divided into four groups that received different doses of PEG-SOD. To assess effects of PEG-SOD on in vitro cultures, four different doses of PEG-SOD were applied to in vitro culture media during in vitro culturing following ovarian tissue vitrification and warming. To evaluate effects of PEG-SOD on ovarian tissue transplantation, four different doses of PEG-SOD were applied for 2, 7, and 21 days to mice following vitrified-warmed mouse ovarian tissue autotransplantation. RESULTS: The percentage of primordial follicles was maintained at the highest dose of PEG-SOD for 2 h in vitro, and there was a significant decrease in the percentage of apoptotic follicles at 2 h, but not at later time points. The highest dose of PEG-SOD also maintained primordial, primary, and secondary follicles 2 days post-transplantation, but only primordial follicles were maintained up to 21 days after transplantation. CONCLUSIONS: PEG-SOD is protective mainly toward primordial follicles only for a short interval in vitro, presumably via antioxidant effects. PEG-SOD may be a promising additive for preserving ovarian tissue integrity, at least for primordial follicles, up to 21 days post-transplantation.

Gender Differences in the Association between Workplace Bullying and Depression among Korean Employees.

Workplace bullying is a prevalent issue with a significant impact on employees' mental health. This study aimed to explore the relationship between workplace bullying and the prevalence of depression, with a particular focus on the role of gender. A total of 12,344 Korean employees aged 19-65 years were included in the study. They completed the Center for Epidemiologic Studies Depression Scale (CES-D) and a score of 16 or higher in CES-D indicated depression. The association between workplace bullying and depression was analyzed using logistic regression analyses. The average CES-D scores were higher for both male and female employees who experienced bullying than for those who did not (p < 0.001). The association between the experience of workplace bullying and the prevalence of depression was statistically significant for both genders, with a stronger correlation observed among male employees (p for interaction < 0.001). Organizations are urged to address workplace bullying, particularly for male employees, through the implementation of anti-bullying strategies and policies, as well as the provision of mental health resources and support.

Compact SPICE Model of Memristor with Barrier Modulated Considering Short- and Long-Term Memory Characteristics by IGZO Oxygen Content.

This paper introduces a compact SPICE model of a two-terminal memory with a Pd/Ti/IGZO/p+-Si structure. In this paper, short- and long-term components are systematically separated and applied in each model. Such separations are conducted by the applied bias and oxygen flow rate (OFR) during indium gallium zinc oxide (IGZO) deposition. The short- and long-term components in the potentiation and depression curves are modeled by considering the process (OFR of IGZO) and bias conditions. The compact SPICE model with the physical mechanism of SiO2 modulation is introduced, which can be useful for optimizing the specification of memristor devices.

Effect of Post-Annealing on Barrier Modulations in Pd/IGZO/SiO2/p+-Si Memristors.

In this article, we study the post-annealing effect on the synaptic characteristics in Pd/IGZO/SiO2/p+-Si memristor devices. The O-H bond in IGZO films affects the switching characteristics that can be controlled by the annealing process. We propose a switching model based on using a native oxide as the Schottky barrier. The barrier height is extracted by the conduction mechanism of thermionic emission in samples with different annealing temperatures. Additionally, the change in conductance is explained by an energy band diagram including trap models. The activation energy is obtained by the depression curve of the samples with different annealing temperatures to better understand the switching mechanism. Moreover, our results reveal that the annealing temperature and retention can affect the linearity of potentiation and depression. Finally, we investigate the effect of the annealing temperature on the recognition rate of MNIST in the proposed neural network.

Does duration of cryostorage affect survival rate, pregnancy, and neonatal outcomes? Large-scale single-center study of slush nitrogen (SN2 ) vitrified-warmed blastocysts.

OBJECTIVE: To evaluate the effects of the duration of cryostorage on clinical outcomes after embryo transfer of vitrified blastocysts stored in an open-device slush-nitrogen (SN2 ) system. METHODS: A retrospective cohort study was carried out on 1632 autologous vitrified-warmed blastocyst transfer cycles between January 2013 and June 2014. Duration of cryostorage was divided into four groups: Group I: 0-6 months (n=937); Group II: 7-12 months (n=299); Group III: 13-24 months (n=165); and Group IV: ≥25 months (n=231). The effects of the duration of cryostorage on the survival rate (SR), clinical pregnancy rate (CPR), live birth rate (LBR), and neonatal outcomes of vitrified blastocysts stored in an open-device SN2 system were evaluated. RESULTS: There were no significant differences between groups in SR, CPR, LBR, and neonatal outcomes after autologous vitrified-warmed blastocyst transfer. Multivariate logistic regression analysis showed no effect on LBR from duration of cryostorage. CONCLUSION: Vitrification using SN2 and long-term cryostorage in an open-device system are safe and effective and do not significantly affect clinical outcomes after embryo transfer.

The Ratio of Mitochondrial DNA to Genomic DNA Copy Number in Cumulus Cell May Serve as a Biomarker of Embryo Quality in IVF Cycles.

Previous studies have reported that the mitochondrial DNA (mtDNA) contents of cumulus cells (CCs) in ovarian follicular fluid are correlated with embryo quality. Quantification of mtDNA CCs has been suggested as a biomarker of embryo viability. The aim of this study was to determine the relationship between mitochondrial DNA (mtDNA)/genomic DNA (gDNA) ratio in CCs and IVF outcomes such as fertilization rates and embryo quality in infertile women. This is an observational study on 144 cumulus-oocyte complexes obtained from 144 patients undergoing IVF-intracytoplasmic sperm injection (ICSI) at a single fertility center. The CCs in ovarian follicular fluid from patients undergoing IVF-ICSI were collected by ovum pick-up. A relative copy number quantification was used to determine mtDNA/gDNA ratio. Quantitative real-time PCR for various markers (ß2M and mtMinArc gene) was used to determine average mtDNA/gDNA ratio of CCs. Investigation of the correlation between mtDNA/gDNA ratio in CCs and IVF outcomes showed no statistically significant correlation between the mtDNA/gDNA ratio in CCs and fertilization rates. However, mtDNA/gDNA ratio and embryo quality showed a statistically significant positive correlation. A significantly higher mtDNA/gDNA ratio was observed in the good quality embryo group compared with the poor quality embryo group (P < 0.05). In addition, the mtDNA/gDNA ratio showed negative correlation with the patient's age (correlation coefficient= -0.228, P < 0.05). Results of this study demonstrate a negative correlation of mtDNA/gDNA ratio in CCs with patient's age, and a low copy number of mtDNA in CCs may have adverse effects on embryo quality in IVF cycles. These results suggest that the ratio of mtDNA/gDNA in CCs may serve as a biomarker in predicting IVF outcomes.